Medicinal chemistry

Medicinal or pharmaceutical chemistry is a discipline at the intersection of chemistry and pharmacology involved with designing, synthesizing and developing pharmaceutical drugs. Medicinal chemistry involves the identification, synthesis and development of new chemical entities suitable for therapeutic use. It also includes the study of existing drugs, their biological properties, and their quantitative structure-activity relationships (QSAR). Pharmaceutical chemistry is focused on quality aspects of medicines and aims to assure fitness for the purpose of medicinal products.

Compounds used as medicines are overwhelmingly organic products. However, metal-containing compounds have been found to be useful as drugs. For example, the cis-platin series of platinium-containing complexes have found use as anti-cancer agents. This type of compounds are known as metal-based drugs.
Medicines can be small organic molecules or biopolymers.

Medicinal chemistry is a highly interdisciplinary science combining organic chemistry with biochemistry, computational chemistry, pharmacology, pharmacognosy, molecular biology, statistics, and physical chemistry.

Fold

Table of Contents

Process of drug discovery

Discovery

Optimization

Development

Training in medicinal chemistry

References

Medicinal Chemistry Topics

Process of drug discovery

Discovery

The first step of drug discovery involves the identification of new active compounds, often called "hits", which are typically found by screening many compounds for the desired biological properties. While a number of approaches toward the identification of hits exist, the most successful of techniques relies on chemical and biological intuition developed through years of rigorous chemical-biological training. Other sources of hits can come from natural sources, such as plants, animals, or fungi. Hits may originate also from random chemical libraries, such as those created through combinatorial chemistry or historic chemical compound collections that are tested en-masse against the biological target in question.

Optimization

Another step in drug discovery involves further chemical modifications in order to improve the biological and physiochemical properties of a given candidate compound library. Chemical modifications can improve the recognition and binding geometries (pharmacophores) of the candidate compounds, their affinities and pharmacokinetics, or indeed their reactivity and stability during their metabolic degradation. A number of methods have contributed to quantitative metabolic prediction, and a recent example is SPORCalc[1].The quantitative structure-activity relationship (QSAR) of the pharmacophore play an important part in finding lead compounds, which exhibit the most potency, most selectivity, best pharmacokinetics and least toxicity. QSAR involves mainly physical chemistry and molecular docking tools (CoMFA and CoMSIA), that leads to tabulated data and first and second order equations. There are many theories, the most relevant being Hansch's analysis that involves Hammett electronic parameters, steric parameters and logP(lipophilicity) parameters.

Development

The final step involves the rendering the lead compounds suitable for use in clinical trials. This involves the optimization of the synthetic route for bulk production, and the preparation of a suitable drug formulation.

Training in medicinal chemistry

Many workers in the field do not have formal training in medicinal chemistry. Graduate (postgraduate) level programs do exist in medicinal chemistry, but frequently the broader education in a chemistry graduate program can provide many of the skills needed.

References

1. ^ James Smith; Viktor Stein (2009). "SPORCalc: A development of a database analysis that provides putative metabolic enzyme reactions for ligand-based drug design". Computational Biology and Chemistry 33 (2): 149-159. doi:10.1016/j.compbiolchem.2008.11.002. PMID 19157988.